Method and system for vacuum driven mass spectrometer interface with adjustable resolution and selectivity

ABSTRACT

A mass spectrometer system and a method of operating same are provided. The system comprises a) an ion conduit for receiving ions; b) a boundary member defining a curtain gas chamber containing the ion conduit; c) a curtain gas supply for providing a curtain gas directed by the boundary member to an inlet of the ion conduit to provide a gas flow into the ion conduit, and a curtain gas outflow out of a curtain gas chamber inlet; d) a mass spectrometer at least partially sealed to, and in fluid communication with, the ion conduit for receiving the ions from the ion conduit; a vacuum chamber surrounding the mass spectrometer operable to draw the gas flow including the ions through the ion conduit and into the vacuum chamber; and, e) a gas outlet for drawing a gas outflow from the gas flow located between the ion conduit and the mass spectrometer to increase the gas flow rate through the ion conduit.

This is a continuation-in-part of U.S. application Ser. No. 12/473,859filed on May 28, 2009, which in turn claims priority from U.S.provisional application No. 61/057,242 filed May 30, 2008 and U.S.provisional application No. 61/178,675 filed May 15, 2009. The contentsof U.S. application Ser. Nos. 12/473,859, 61/057,242 and 61/178,675 areincorporated herein by reference.

INTRODUCTION

The present invention relates generally to methods and systems involvingboth a mass spectrometer and a differential mobility spectrometer.

In differential mobility spectrometer/mass spectrometer systems, a driftgas is typically supplied from a compressed gas source upstream of thedifferential mobility spectrometer. This drift gas acts as a carrier gasflow through the differential mobility spectrometer. The delivery of thedrift gas to the differential mobility spectrometer can be controlled byflow restriction valves. Sensitivity is related to the transmissionefficiency of the system—what percentage of the ions end up beingactually detected. Selectivity or resolution refers to the detector'sability to distinguish between similar ions.

Differential mobility spectrometry, also referred to as high fieldasymmetric waveform ion mobility spectrometry (FAIMS) or Field IonSpectrometry (FIS), is a variant of ion mobility spectrometry (IMS). IMSseparates ions by the difference in the time it takes for them to driftthrough a gas, typically at atmospheric pressure, in a constantelectrostatic field of low field strength applied along the axial lengthof a flight tube. Ions are pulsed into the flight tube and their flighttimes are recorded. The time of flight is inversely related to themobility of an ion. Ions have a single motion of direction (axial) andare separated according to their mobility through the gas under theselow field conditions (E<1000V/cm). The drift time and thus mobility is afunction of the size and shape of an ion and its interactions with thebackground gas.

Differential mobility spectrometry differs from IMS in the geometry ofthe instrumentation and adds an additional dimension to the separationtheory. RF voltages, often referred to as separation voltages (SV), areapplied across the ion transport chamber, perpendicular to the directionof the transport gas flow. Ions will migrate toward the walls and leavethe flight path unless their trajectory is corrected by acounterbalancing voltage, a DC potential often referred to as acompensation voltage (CV). Instead of recording the flight time of anion through the chamber, the voltage required to correct the trajectoryof a particular ion is recorded. Ions are not separated in time as withan IMS: instead, the mobility measurement is a function of thecompensation voltage used to correct the tilt in ion trajectory causedby the difference between high field and low field ion mobilities. Assuch, ions are not pulsed into the analyzer but instead introduced in acontinuous fashion and the compensation voltage is scanned to seriallypass ions of different differential mobility or set to a fixed value topass only ion species with a particular differential mobility.

SUMMARY OF THE INVENTION

Typically, there is a tradeoff between selectivity and sensitivity, bothof which are linked to the residence time of the ions in thedifferential mobility spectrometer. Specifically, increasing theresidence time of the ions in the differential mobility spectrometer mayincrease selectivity, but at the price of reducing sensitivity.

As described above, in the description that follows, sensitivity isrelated to the transmission efficiency of the system—what percentage ofthe ions end up being actually detected. Selectivity or resolutionrefers to the detector's ability to distinguish between similar ions.

In accordance with an aspect of an embodiment of the invention, there isprovided a mass spectrometer system comprising:

-   a) an ion conduit for receiving ions from an ion source, the ion    conduit having an internal operating pressure;-   b) a boundary member defining a curtain gas chamber containing the    ion conduit;-   c) a curtain gas supply for providing a curtain gas directed by the    boundary member to an inlet of the ion conduit to dry and decluster    the ions and to provide a gas flow into the ion conduit, and a    curtain gas outflow out of a curtain gas chamber inlet;-   d) a mass spectrometer at least partially sealed to, and in fluid    communication with, the ion conduit for receiving the ions from the    ion conduit;-   e) a vacuum chamber surrounding the mass spectrometer for    maintaining the mass spectrometer at a vacuum pressure lower than    the internal operating pressure, such that the vacuum chamber is    operable to draw the gas flow including the ions through the ion    conduit and into the vacuum chamber; and,-   f) a gas outlet for drawing a gas outflow from the gas flow located    between the ion conduit and the mass spectrometer to increase the    gas flow rate through the ion conduit, the gas outlet being located    between the ion conduit and the mass spectrometer.

In accordance with an aspect of another embodiment of the invention,there is provided a method of operating a mass spectrometer systemincluding an ion conduit contained in a curtain gas chamber, and a massspectrometer contained in a vacuum chamber at least partially sealed to,and in fluid communication, with, the ion conduit. The method comprises:

-   a) maintaining the ion conduit at an internal operating pressure by    directing a curtain gas to an inlet of the ion conduit to dry and    decluster the ions and to provide a gas flow into the ion conduit;-   b) providing a curtain gas outflow out of a curtain gas chamber    inlet of the curtain gas chamber;-   c) providing ions to the ion conduit;-   d) maintaining the mass spectrometer at a vacuum pressure lower than    the internal operating pressure to draw the gas flow including the    ions through the ion conduit and into the vacuum chamber; and, e)    drawing a bleed gas at a bleed gas flow rate from the gas flow    between the ion conduit and the mass spectrometer to increase a gas    flow rate through the ion conduit.

BRIEF DESCRIPTION OF THE DRAWINGS

The skilled person in the art will understand that the drawings,described below, are for illustration purposes only. The drawings arenot intended to limit the scope of the applicant's teachings in any way.

FIG. 1, in a schematic diagram, illustrates a differential mobilityspectrometer/mass spectrometer system including a juncture chamber towhich a throttle gas is added between the differential mobilityspectrometer and the mass spectrometer in accordance with an aspect of afirst embodiment of the present invention.

FIG. 2, in a schematic view, illustrates a differential mobilityspectrometer/mass spectrometer system including a juncture chamber towhich a throttle gas is added between the differential mobilityspectrometer and the mass spectrometer in accordance with an aspect of asecond embodiment of the present invention.

FIG. 2A, in a graph, plots the signals for various ions against the DMSoffset potential relative to a potential at the vacuum chamber inlet ormass spectrometer inlet.

FIG. 3, in a schematic view, illustrates a differential mobilityspectrometer/mass spectrometer system including a juncture chamber towhich a throttle gas is added between the differential mobilityspectrometer and the mass spectrometer, and in which gas flow into thedifferential mobility spectrometer is restricted, in accordance with anaspect of a third embodiment of the present invention.

FIG. 4, in a schematic view, illustrates a differential mobilityspectrometer/mass spectrometer system in which a controlled leak isprovided at a juncture of the differential mobility spectrometer and themass spectrometer to adjust the gas flow rate through the differentialmobility spectrometer in accordance with an aspect of a fourthembodiment of the present invention.

FIG. 5, in a schematic view, illustrates a differential mobilityspectrometer/mass spectrometer system including a juncture chamber towhich the throttle gas is added between the differential mobilityspectrometer and the mass spectrometer and in which the differentialmobility spectrometer includes a heated tube in accordance with anaspect of a fifth embodiment of the present invention.

FIG. 6, in a schematic view, illustrates a differential mobilityspectrometer/mass spectrometer system similar to that described in FIG.2, and in which bubblers are provided for adding liquid modifiers to thecurtain gas provided to the curtain chamber, in accordance with anaspect of a sixth embodiment of the present invention.

FIG. 7, in a schematic view, illustrates a differential mobilityspectrometer/mass spectrometer system similar to that of FIG. 6, butalso including an additional conduit branch for providing curtain gasdirectly to the curtain chamber without any liquid modifiers, inaccordance with an aspect of a seventh embodiment of the presentinvention.

FIG. 8, in a schematic view, illustrates a differential mobilityspectrometer/mass spectrometer system including a juncture chamber towhich a throttle gas is added between the differential mobilityspectrometer and the mass spectrometer, and in which bubblers areprovided to add various modifiers to the throttle gas, in accordancewith an aspect of a eighth embodiment of the present invention.

FIG. 9, in a schematic view, illustrates a differential mobilityspectrometer/mass spectrometer system including a juncture chamber fromwhich a bleed gas is drawn between the differential mobilityspectrometer and the mass spectrometer in accordance with an aspect of aninth embodiment of the present invention.

FIG. 10, in a series of graphs, illustrates different resolutions of aCV scan for separation of a sample containing ephedrine andpseudoephedrine using a fixed differential mobility spectrometergeometry with a variable amount of throttle gas added at the juncture ofthe differential mobility spectrometer and the mass spectrometer.

FIG. 11, in a schematic view, illustrates a mass spectrometer systemincluding a juncture chamber from which a bleed gas is drawn between anupstream heated tube and a downstream mass spectrometer in accordancewith an aspect of a tenth embodiment of the present invention.

FIG. 12, in a schematic view, illustrates a mass spectrometer systemincluding a juncture chamber from which a bleed gas is drawn between anupstream heated tube and a downstream mass spectrometer, wherein anelectric field is provided within the juncture chamber to guide ionsinto the mass spectrometer and to impede ions from being drawn out ofthe juncture chamber with the bleed gas in accordance with an aspect ofa further embodiment of the invention.

DESCRIPTION OF VARIOUS EMBODIMENTS

Referring to FIG. 1, there is illustrated in a schematic view, adifferential mobility spectrometer/mass spectrometer system 200 inaccordance with an aspect of a first embodiment of the presentinvention. The differential mobility spectrometer/mass spectrometersystem 200 comprises a differential mobility spectrometer 202 and afirst vacuum lens element 204 of a mass spectrometer (hereinaftergenerally designated mass spectrometer 204). Mass spectrometer 204 alsocomprises mass analyzer elements 204 a downstream from vacuum chamber227. Ions can be transported through vacuum chamber 227 and may betransported through one or more additional differentially pumped vacuumstages prior to the mass analyzer indicated schematically as massanalyzer elements 204 a. For instance in one embodiment, a triplequadrupole mass spectrometer may comprise three differentially pumpedvacuum stages, including a first stage maintained at a pressure ofapproximately 2.3 Torr, a second stage maintained at a pressure ofapproximately 6 mTorr, and a third stage maintained at a pressure ofapproximately 10⁻⁵ Torr. The third vacuum stage may contain a detector,as well as two quadrupole mass analyzers with a collision cell locatedbetween them. It will be apparent to those of skill in the art thatthere may be a number of other ion optical elements in the system thathave not been described. This example is not meant to be limiting as itwill also be apparent to those of skill in the art that the differentialmobility spectrometer/mass spectrometer coupling described can beapplicable to many mass spectrometer systems that sample ions fromelevated pressure sources. These may include time of flight (TOF), iontrap, quadrupole, or other mass analyzers as known in the art.

The differential mobility spectrometer 202 comprises plates 206 and anelectrical insulator 207 along the outside of plates 206. The plates 206surround a drift gas 208 that drifts from an inlet 210 of thedifferential mobility spectrometer to an outlet 212 of the differentialmobility spectrometer 202. The insulator 207 supports the electrodes andisolates them from other conductive elements. For example, the insulatormay be fabricated from ceramic or Teflon™. The outlet 212 of thedifferential mobility spectrometer 202 releases the drift gas into ajuncture or baffle chamber 214 defined by baffles 216, which juncturechamber 214 defines a path of travel for ions between the differentialmobility spectrometer 202 and the mass spectrometer 204. In someembodiments, the outlet 212 of the differential mobility spectrometer202 is aligned with the inlet of the mass spectrometer 204 to define theion path of travel therebetween, while the baffles 216 are spaced fromthis path of travel to limit interference of the baffles 216 with theions 222 traveling along the path of travel.

The differential mobility spectrometer 202 and juncture chamber 214 areboth contained within a curtain chamber 218, defined by curtain plate(boundary member) 219 and supplied with a curtain gas from a curtain gassource 220. The curtain gas source 220 provides the curtain gas to theinterior of the curtain chamber 218. Ions 222 are provided from an ionsource (not shown) and are emitted into the curtain chamber 218 viacurtain chamber inlet 224. The pressure of the curtain gas within thecurtain chamber 218 provides both a curtain gas outflow 226 out ofcurtain gas chamber inlet 224, as well as a curtain gas inflow 228 intothe differential mobility spectrometer 202, which inflow 228 becomes thedrift gas 208 that carries the ions 222 through the differentialmobility spectrometer 202 and into the juncture chamber 214. The curtainplate 219 may be connected to a power supply to provide an adjustable DCpotential to it.

As illustrated in FIG. 1, the first vacuum lens element 204 of the massspectrometer 204 is contained within a vacuum chamber 227, which can bemaintained at a much lower pressure than the curtain chamber 218. Inaccordance with an aspect of an embodiment of the present invention, thevacuum chamber 227 can be maintained at a pressure of 2.3 Torr by avacuum pump 230 while the curtain chamber 218 and an internal operatingpressure of the differential mobility spectrometer 202 can be maintainedat a pressure of 760 Torr. As a result of the significant pressuredifferential between the curtain chamber 218 and the vacuum chamber 227,the drift gas 208 is drawn through the differential mobilityspectrometer 202, the juncture chamber 214 and, via vacuum chamber inlet229, into the vacuum chamber 227 and first vacuum lens element 204. Asshown, the mass spectrometer 204 can be sealed to (or at least partiallysealed), and in fluid communication with the differential mobilityspectrometer, via the juncture chamber, to receive the ions 222 from thedifferential mobility spectrometer 202.

As shown, the baffles 216 of the curtain chamber comprise a controlledleak or gas port 232 for admitting the curtain gas into the juncturechamber 214. Within the juncture chamber 214, the curtain gas becomes athrottle gas that throttles back the flow of the drift gas 208 throughthe differential mobility spectrometer 202. Specifically, the throttlegas within the juncture chamber 214 modifies a gas flow rate within thedifferential mobility spectrometer 202 and into the juncture chamber214, thereby controlling the residence time of the ions 222 within thedifferential mobility spectrometer 202. By controlling the residencetime of the ions 222 within the differential mobility spectrometer 202,resolution and sensitivity can be adjusted. That is, increasing theresidence times of the ions 222 within the differential mobilityspectrometer 202 can increase the resolution, but can also result inadditional losses of the ions, reducing sensitivity. In some embodimentsit can therefore be desirable to be able to precisely control the amountof throttle gas that is added to the juncture chamber 214 to provide adegree of control to the gas flow rate through the differential mobilityspectrometer 202, thereby controlling the tradeoff between sensitivityand selectivity. In the embodiment of FIG. 1, the inflow of throttle gasfrom the curtain chamber 218 can be controlled by controlling the sizeof the leak provided by the gas port 232.

The baffles can be configured to provide a randomizer surface member,and the gas port 232 can be oriented to direct the throttle gas at leastsomewhat against the baffles 216 and randomizer surface to disburse thethrottle gas throughout the juncture chamber 214. In one embodiment, thegas port 232 introduces the throttle gas without disrupting the gasstreamlines between the differential mobility spectrometer 202 and themass spectrometer inlet 229.

As described above and as known in the art, RF voltages, often referredto as separation voltages (SV), can be applied across an ion transportchamber of a differential mobility spectrometer perpendicular to thedirection of drift gas 208 (shown in FIG. 1). The RF voltages may beapplied to one or both of the DMS electrodes comprising the differentialmobility spectrometer. The tendency of ions to migrate toward the wallsand leave the path of the DMS can be corrected by a DC potential oftenreferred to as a compensation voltage (CV). The compensation voltage maybe generated by applying DC potentials to one or both of the DMSelectrodes comprising the differential mobility spectrometer. As isknown in the art, a DMS voltage source (not shown) can be provided toprovide both the RF SV and the DC CV. Alternatively, multiple voltagesources may be provided.

Similarly, a DC declustering or inlet potential can be provided to thevacuum chamber inlet 229 (again as shown in FIG. 1) by an inletpotential voltage source (not shown), again as known in the art. Thisvacuum chamber inlet may be a orifice, or, alternatively, may be acapillary, heated, capillary or an ion pipe.

In embodiments of the present invention in which the vacuum chamberinlet 229 is smaller then an outlet of the differential mobilityspectrometer 202, it can be advantageous to provide a braking potentialto the vacuum chamber inlet 229 relative to the differential mobilityspectrometer 202. This braking potential can be provided by providing aDMS DC offset voltage to the plates or electrodes of the DMS relative tothe declustering or inlet potential provided to the vacuum chamber inlet229. By slowing down the ions prior to them entering the vacuum chamber229, the braking potential can increase the extent to which these ionsare entrained within the gas flows, thereby increasing the likelihoodthat the ions will actually pass through the vacuum chamber inlet,instead of impacting on the sides of the vacuum chamber inlet 229.

Alternatively, in some embodiments of the present invention, such as,for example without limitation, embodiments in which the vacuum chamberinlet 229 is larger relative to the slit or outlet from the differentialmobility spectrometer 202, it can be desirable to adjust the DMS DCoffset voltage. In particular this DC offset voltage may actually bepositive to speed up ions as they pass through the vacuum chamber inlet229, if it is not desirable to slow them down to improve transmissionfrom the differential mobility spectrometer 202 into the vacuum chamber227.

This DMS DC offset can also be adjusted based on a mass of the ionsbeing selected in a differential mobility spectrometer 202. This couldbe part of a two-stage process. Specifically, the declustering voltageprovided to the vacuum chamber inlet 229 can first be adjusted based onthe mass of the ions being selected in the differential mobilityspectrometer 202. Then, relative to this declustering potential providedto the vacuum chamber inlet 229, the DMS DC offset voltage could beadjusted to enhance transmission from the differential mobilityspectrometer 202 through the vacuum chamber inlet 229. Alternatively,the DMS offset DC potential may be selected for a given ion. In someembodiments, a voltage source controller can be set to automaticallyadjust the DMS electrode DC offsets to maintain the same potentialdifference relative to the orifice potential. Then the declusteringpotential or inlet potential may be adjusted, That is, in theseembodiments the DMS offset voltage is merely the difference between theDC potential applied to the electrodes as an offset and the inletvoltage. Say, for example, that a preferred DMS offset voltage is −3 V.Then, when the inlet voltage is tuned, the control system can, in theseembodiments, maintain that −3 V offset regardless of the current inletvoltage. For instance, if the inlet potential is initially 50 V, the DCpotential on the DMS electrodes can be automatically maintained at 47 V(CV=0 situation). If the inlet potential is tuned up to 100 V, the DCapplied to the DMS electrodes can be automatically changed to 97 V. TheCV=0 situation means that an ion high and low field mobility are eitherthe same, or extremely similar. This may occur if the separation voltageis 0 V, or under some conditions with the separation voltage applied.

Referring to FIG. 2, there is illustrated in a schematic view, adifferential mobility spectrometer/mass spectrometer system 300 inaccordance with an aspect of a second embodiment of the presentinvention. For clarity, the same reference numerals used in FIG. 1, with100 added, are used in FIG. 2 to designate elements analogous to theelements of FIG. 1. For brevity, the description of FIG. 1 is notrepeated with respect to FIG. 2.

It is important to note that due to the compensation voltage provided tothe plates or electrodes of the differential mobility spectrometer, theactual DC potential of one or both of the electrodes of the differentialmobility spectrometer may not differ by the DMS DC offset amount fromthe declustering potential applied to vacuum chamber inlet element. Forexample, say that a declustering potential is applied to vacuum chamberinlet element 329. This declustering potential (DP) is determined basedon the m/z of the ion being selected by the differential mobilityspectrometer, and this determination of the DP is known in the art.Then, a DC offset voltage is applied to the plate or electrodes 306 ofthe differential mobility spectrometer 302. In addition, the CV will beapplied to the electrodes 306. Application of a CV may proceed indifferent ways. For example, say that there is a CV of 10 volts, then 5Vcan be applied to one electrode, while −5V are applied to the otherelectrode. Alternatively, 10V can be applied to one electrode and novolts to the other electrode.

Consider an example where all of the CV is applied to one electrode.Then, say that a DP of 100V is first determined for the vacuum chamberinlet. The offset between the vacuum chamber inlet and the differentialmobility spectrometer is determined to be −5V. The CV for thedifferential mobility spectrometer is 10V. Then, one electrode of thedifferential mobility spectrometer would have a potential of 100V−5V+10Vor 105V, while the other electrode would have a potential of100V−5V=95V.

As noted above, the DC offset voltage need not be negative.Specifically, where the orifice or inlet dimension more closely matchesthe slit dimension for the differential mobility spectrometer, there maybe no need to slow the ions down to properly entrain them in the gasflow so that they can flow through the orifice. Instead, it could evenbe desirable to speed the ions up.

Referring to FIG. 2A, the effectiveness of braking potentials applied toelectrodes of dimension 1×10×30 mm is plotted in a graph for variousmass to charge ratios. For all the ions tested, the optimal DMS offsetvoltage appears to be negative—that is, the optimal DMS potential shouldbe slightly lower than the vacuum chamber inlet potential to establish abraking potential. The magnitude of the optimal offset voltage and thewidths of the optimal voltage range both increase with the mass tocharge ratio of the ion of interest, likely reflecting the knowndecrease in the ion mobility constant for higher m/z ions. The dataplotted in FIG. 2A demonstrates that the transfer of ions from a slottedDMS analyzer to a circular mass spectrometer or vacuum chamber inlet maybe improved by slowing down the ions to give them a longer time periodin which to be influenced by the bending gas streams converging on theinlet, thereby reducing losses in the interface region or juncture ofthe differential mobility spectrometer and mass spectrometer.

As with the system 200 of FIG. 1, in the system 300 of FIG. 2 drift gas308 can be drawn through the differential mobility spectrometer 302 andinto the vacuum chamber 327 and the first vacuum lens element 304 by themuch lower pressure maintained in the vacuum chamber 327. As with thesystem 200 of FIG. 1, the vacuum chamber 327 of the system 300 can bemaintained, say, at a pressure of 2.3 Torr, for example, while thepressure in the curtain chamber 318 can be maintained at a pressure of760 Torr.

As with the system 200 of FIG. 1, the resolution or selectivity ofsystem 300 can be adjusted by adding a throttle gas to a juncturechamber 314 between the differential mobility spectrometer 302 and thevacuum chamber inlet 329. In the system 300 of FIG. 2, a common sourceis provided for both the curtain gas and the throttle gas; however,separate sources may also be provided. For example, this gas could benitrogen. The throttle gas flows through a conduit branch 320 a into thejuncture chamber 314. Again, this gas is called a throttle gas becauseit throttles back the flow through the differential mobilityspectrometer. In some embodiments, the gas can be added in a coaxialmanner to reduce the likelihood of a cross beam of the throttle gasinterfering with the ion beam trajectory or ion path of travel betweenthe differential mobility spectrometer 302 and the mass spectrometer, asinterference with this ion beam trajectory could potentially diminishtransmission efficiency. For example, as shown in FIG. 2, gas ports 332are oriented or inclined such that the throttle gas flows into thejuncture chamber 314 at an orientation that is toward the vacuum chamber327 and away from the differential mobility spectrometer 302.Optionally, the juncture chamber 314 can be enlarged or may includeextra structures to reduce the linear velocity of the throttle gas toreduce its interference with the ion beam at the point of entry into themass spectrometer. Further, the gas ports 332 may optionally be orientedsuch that the throttle gas flows along the sidewalls of the juncturechamber, somewhat parallel to the ion path of travel. In anotherembodiment, the juncture chamber may be designed with a much largerdiameter than the diameter of the insulator, and the gas port may beoriented such that the gas stream through the inlet is directed alongthe wall.

Please note that schematic FIGS. 1-9 are not to scale. That is, from afunctional perspective the juncture chamber can be made substantiallylarger than what is shown in the figures, to reduce the risk of thethrottle gas inflow disrupting ion flow through the juncture chamber.Further, the throttle gas can be introduced so as to be directed alongthe wall, thereby reducing disruption, and increasing sensitivity, ascompared to the case in which the throttle gas is provided in across-flow to the ion motion in the juncture chamber.

Conduit branch 320 a comprises a controllable valve 320 b that can beused to control the rate of flow of the throttle gas into the juncturechamber 314. For example, to increase resolution or selectivity, at theprice of an acceptable loss in sensitivity, the controllable valve 320 bcould be opened to admit more throttle gas into the juncture chamber 314via conduit branch 320 a to reduce the gas flow rate within thedifferential mobility spectrometer 302. This, in turn, can increase theresidence time of the ions 322 within the differential mobilityspectrometer. The increased residence time manifests itself as narrowermobility peak widths, and therefore, improved selectivity. At the sametime, the increased residence time lowers sensitivity somewhat due toincreased diffusion losses. At the same time, because of the increasedresidence time within the differential mobility spectrometer, more ofthe ions can be lost.

As shown, FIG. 2 also can comprise a valve 320 c for controlling therate of flow of the curtain gas into the curtain chamber 318. It isimportant to control the curtain gas flow rate to ensure properdeclustering of ions upstream of to the DMS. Clusters can have differentmobilities than dry ions, and can therefore have different compensationvoltage (CV) values. These clusters can be filtered and lost whiletransmitting an ion of interest, leading to reduced sensitivity. Asshown in FIG. 2, the system may comprise a common gas supply to provideboth the curtain gas and the throttle gas flows. The curtain gas outflow326 from the curtain plate 319 aperture can be defined by the sum of thevolumetric flow rates for the curtain gas and the throttle gas minus thevolumetric flow rate through the gas conductance limiting aperture 329.The curtain gas outflow 326 is typically optimized for a given compoundand set of conditions. Therefore, with the configuration illustrated inFIG. 2, the curtain gas outflow 326 may be maintained constantregardless of what portion of the total flow is provided through passage320 (curtain gas) or 320 a (throttle gas), provided that the totalvolumetric flow rate is constant.

As the differential mobility spectrometer 302 is sealed, or at leastpartially sealed (no seal is perfect) to the mass spectrometer, or atleast to the first vacuum chamber 327, The mass spectrometer cancomprise a circular orifice to receive the ions 322 from thedifferential mobility spectrometer 302. This is enabled by thestreamlines resulting from sealing the differential mobilityspectrometer 302 to the mass spectrometer. The gas streamlines exitingthe differential mobility spectrometer 302 converge on the orifice inlet329, and these bending streamlines can transport ions through the inlet329. It can be desirable to maintain a circular orifice to ensure hightransmission efficiency through subsequent vacuum stages and lenses.

Referring to FIG. 3, there is illustrated in a schematic view, adifferential mobility spectrometer/mass spectrometer system 400 inaccordance with an aspect of a third embodiment of the presentinvention. For clarity, the same reference numerals used in FIG. 2, with100 added, are used in FIG. 3 to designate elements analogous to theelements of FIG. 2. For brevity, the descriptions of FIGS. 1 and 2 arenot repeated with respect to FIG. 3.

As with the system 300 of FIG. 2, the resolution or selectivity ofsystem 400 of FIG. 3 can be adjusted by adding throttle gas to ajuncture chamber 414 between the differential mobility spectrometer 402and the vacuum chamber inlet 429. As with system 300 of FIG. 2, a commonsource can be provided for both the curtain gas and the throttle gas.

In addition, gas restriction plates 434 are provided at an inlet 410 ofthe differential mobility spectrometer 402. These gas restriction plates434 can facilitate tuning the pressure of the differential mobilityspectrometer 402 for further optimization of selectivity, in ananalogous fashion to Nazarov et al. (Nazarov E G, Coy S L, Krylov E V,Miller A R, Eiceman G., Pressure Effects in Differential MobilitySpectrometry, Anal. Chem., 2006, 78, 7697-7706). Specifically, when thegas restriction plates 434 are provided to restrict the flow of driftgas into the differential mobility spectrometer 402, pumping at the backof the differential mobility spectrometer 402, by providing the lowerpressure in the vacuum chamber 427, can lower the pressure within thedifferential mobility spectrometer to provide an extra degree ofselectivity or an extra parameter to adjust for tricky separations. Thediameter of the aperture in the gas restriction plate 434 can beadjustable to allow an operator to tune the pressure within thedifferential mobility spectrometer 402 for the vacuum draw establishedwith a fixed mass spectrometer inlet diameter.

Referring to FIG. 4, there is illustrated in a schematic view adifferential mobility spectrometer/mass spectrometer system 500 inaccordance with an aspect of a fourth embodiment of the presentinvention. For clarity, the same reference numerals used in FIG. 1, with300 added, are used in FIG. 4 to designate elements analogous to theelements of FIG. 1. For brevity, the descriptions of FIGS. 1 to 3 arenot repeated with respect to FIG. 4.

The system 500 of FIG. 4 is a hybrid of the systems 200 and 300 of FIGS.1 and 2 respectively. That is, similar to the system 200 in FIG. 1, thecurtain gas supply 520 provides a curtain gas to the curtain chamber518, and a controlled leak 532 is provided from the curtain chamber 518into the juncture chamber 514. However, similar to the system 300 ofFIG. 2, the flow of throttle gas into the juncture chamber 514 of thesystem 500 of FIG. 4 can be controlled independently of the pressure ofthe curtain gas within the curtain chamber 518 by adjusting gas flowrestrictors 533. That is, gas flow restrictors 533 can be adjusted toadjust the size of controlled leak 532, thereby adjusting the amount ofthrottle gas sucked into the juncture chamber 514, without mechanicallybreaking the seal with the mass spectrometer 504. In contrast, thecontrolled leak 232 of the system 200 of FIG. 1 is provided bymechanically altering the leak provided by the seal with the massspectrometer as shown in FIG. 1. Specifically, baffles 216 of the system200 of FIG. 1 are adjustable to control the size of the leak shown inFIG. 1.

Referring to FIG. 5, there is illustrated in a schematic view, adifferential mobility spectrometer/mass spectrometer system 600 inaccordance with an aspect of a fifth embodiment of the invention. Forclarity the same reference numerals used in FIG. 2, with 300 added areused in FIG. 5 to designate elements analogous to the elements of FIG.2. For brevity, the descriptions of FIGS. 1 and 2 are not repeated withrespect to FIG. 5.

In a system 600 of FIG. 5, a heated tube 602 a is installed at the inlet610 of the differential mobility spectrometer 602. The heated tube 602 acan be sealed to the inlet 610 of the differential mobility spectrometer602. The heated tube 602 a can facilitate additional declustering of theions 622 prior to the ions 622 entering the differential mobilityspectrometer. During use with high flow rate high performance liquidchromatography (HPLC), for example clusterring can be a problem thatdecreases sensitivity. This additional declustering can also help withother ion sources, such as atmospheric pressure matrix-assisted laserdesorption/ionization (AP-MALDI), atmospheric pressure chemicalionization (APCI), Desorption electrospray ionization (DESI), and DirectAnalysis in Real Time (DART), for example. While these sources have beenprovided as examples, it will be apparent to those of skill in the artthat this approach can improve performance for any ionization sourcethat generates ions as well as clusters. The heated tube 602 a can alsofacilitate laminar flow conditions, and increase the uniformity of theelectric field at the inlet 610 of the differential mobilityspectrometer 602, and by doing so can facilitate ion transmission intothe differential mobility spectrometer 602.

In some embodiments of the present invention, such as the system 600illustrated in FIG. 5, increases in the volumetric flow of throttle gasinto the juncture chamber 614 can be balanced by correspondingreductions in the volumetric flow rate of curtain gas into the curtainchamber 618. For example, the total rate of flow of, say, nitrogen, intoboth the curtain chamber and the juncture chamber (the curtain gas flowrate and the throttle gas flow rate respectively) can be keptsubstantially constant by balancing changes in one of the curtain gasflow rate and the throttle gas flow rate with opposite changes in theother of these flow rates. This can be desirable.

Specifically, if the flow of throttle gas into the juncture chamber isincreased while the flow of curtain gas into the curtain chamber is keptconstant, then the outflow of curtain gas away from the inlet of thedifferential mass spectrometer can be expected to increase. This can beundesirable. That is, as shown in FIG. 5 for example, a particularoutflow 626 of curtain gas, in the opposite direction to the flow of gasthrough the differential mobility spectrometer and into the massspectrometer, may have been selected for a particular group of ionssharing a common m/z to decluster these ions. Thus, the curtain gasoutflow rate desired may depend on the group of ions of interest andwhat counterflow is desired to help to decluster them. If the flow ofthrottle gas into the juncture chamber 614 is increased, then, otherthings equal, the outflow 626 from the boundary member 619 can also beexpected to increase beyond what was selected, which can be undesirable.Accordingly, in some embodiments it can be desirable to reduce theinflow of the curtain gas into the curtain chamber proportionally tobalance an increase in the inflow of throttle gas into the juncturechamber.

FIG. 5 illustrates one way in which this can be achieved. Specifically,for system 600 a common source is shown for both the curtain gas and thethrottle gas. Thus, for example, if a greater flow from this commonsource is used to increase the rate at which throttle gas flows into thejuncture chamber, then there may be a corresponding reduction in theflow rate of the curtain gas from this common source into the curtainchamber. This reduction of the flow rate of curtain gas into the curtainchamber can help to balance the increase in the rate of flow of throttlegas into the juncture chamber, such that the outflow 626 of curtain gasaway from the inlet of differential mass spectrometer 602 issubstantially unchanged.

This balancing of increases in throttle gas flow with proportionaldecreases in curtain gas flow can also be achieved using other means inconnection with other embodiments of the present invention. For example,in the case of the system 500 of FIG. 4, increasing the curtain gas flowrate into the curtain chamber 518 could, on its own, also increase therate at which throttle gas flows into the juncture chamber 514,resulting in a significant increase in the outflow 526 from the boundarymember 519 relative to the outflow initially selected. However, thiseffect can be overcome, and the rate at which throttle gas flows intothe juncture chamber even reduced, by adjusting gas flow restrictors 533to reduce the flow of throttle gas into the juncture chamber 514 viacontrolled leak 532. Of course, where the throttle gas flow ratedecreases, the curtain gas flow into the curtain chamber can beproportionally increased, to maintain the outflow of curtain gas awayfrom the inlet of the differential mass spectrometer substantiallyconstant.

Referring to FIG. 6, there is illustrated in a schematic view adifferential mobility spectrometer/mass spectrometer system 700 inaccordance with an aspect of a sixth embodiment of the presentinvention. For clarity, the same reference numerals used in FIG. 2, with400 added, are used in FIG. 6 to designate elements analogous to theelements of FIG. 2. For brevity the descriptions of preceding Figures,including FIGS. 1 and 2, are not repeated with respect to FIG. 6.

As shown in FIG. 6, the system 700 is quite similar to the system 300 ofFIG. 2. However, the system 700 of FIG. 6 comprises additional elements.Specifically, as with the system 300 of FIG. 2, a curtain gas supply 720comprises a controllable valve 720 b that can be used to control therate of flow of the throttle gas into the juncture chamber 714 viaconduit branch 720 a. Conduit or curtain gas supply 720 also comprises avalve 720 c for controlling the rate of flow of the curtain gas thatwill ultimately end up in the curtain chamber 718. The flow of thecurtain gas downstream of valve 720 c is divided into two branches 720 dand 720 e. The flow of the curtain gas within branch 720 d is controlledby valve 720 f. Similarly, the flow of the curtain gas within branch 720e is controlled by valve 720 g.

The flow of the curtain gas through branch 720 d passes into a bubbler720 h, which can be used to add a modifier liquid to the curtaingas/drift gas, which passes through branch 720 d and will ultimately bepumped into the differential mobility spectrometer 702 by the vacuummaintained in the vacuum chamber 727. Similarly, a separate modifier canbe added to the curtain gas flowing through branch 720 e in bubbler 720i. The curtain gas outflows from the bubblers 720 h and 720 i can becontrolled by outlet valves 720 j and 720 k respectively, after whichthe two branches 720 d and 720 e merge and then release the curtain gaswith the modifiers into the curtain chamber 718. As noted above, thecurtain gas and drift gas are one and the same; thus, adding themodifiers to the curtain gas adds simplicity to the system 700.Modifiers can be vapors that provide selectivity by clustering with ionsto different degrees, thereby shifting the differential mobility.Examples of modifiers can include alcohols such as isopropyl alcohol,water, as well as hydrogen and deuterium exchange agents, such asdeuterated water or methanol, which can be used, amongst other things,to count the number of exchangeable protons on a molecule. In general, amodifier may be defined as any additive to the drift gas that changesthe observed compensation voltage for a peak at a given AC amplitude.The compensation voltage is related to the ratio of high to low fieldmobility. Modifiers can act in other ways as well as clusteringphenomena. For instance, changing the polarizability of the drift gascan also change the observed compensation voltage. Clustering andpolarizability changes are two examples of mechanisms that modifiers mayuse to change compensation voltage optima; however, there may also bemany other mechanisms.

Referring to FIG. 7, there is illustrated in a schematic view adifferential mobility spectrometer/mass spectrometer system 800 inaccordance with an aspect of a seventh embodiment of the presentinvention. For clarity, the same reference numerals used in FIG. 6 with100 added are used in FIG. 7 to designate elements analogous to theelements of FIG. 6. For brevity the descriptions of preceding figures,including FIGS. 1, 2 and 6, are not repeated with respect to FIG. 7.

As shown in FIG. 7, the system 800 is very similar to the system 700 ofFIG. 6. However the system 800 of FIG. 7 comprises an additional conduitbranch 821. Conduit branch 821 can provide curtain gas, nitrogen in thepresent case, directly to the curtain chamber 818 without passingthrough bubblers 820 h and 820 i for modifier liquids to be added.Alternatively conduit branch 821 can provide curtain gas directly tochamber 818, while an additional gas fraction can also be addedcontaining one or more modifiers.

Referring to FIG. 8, there is illustrated in a schematic view adifferential mobility spectrometer/mass spectrometer system 900 inaccordance with an aspect of an eighth embodiment of the presentinvention. For clarity, the same reference numerals used in FIG. 2, with600 added, are used in FIG. 8 to designate elements analogous to theelements of FIG. 2. For brevity, the descriptions of preceding figures,including FIGS. 1 and 2 are not repeated with respect to FIG. 8.

As shown in FIG. 8, the system 900 is quite similar to the system 300 inFIG. 2. However, the system 900 in FIG. 8 comprises additional elements.Specifically, as with the system 300 of FIG. 2, a curtain gas supply 920comprises a controllable valve 920 c for controlling the rate of flow ofthe curtain gas into curtain chamber 918. However, unlike theembodiments of FIGS. 2 and 7, separate sources are provided for thecurtain gas and the throttle gas. Specifically, the system 900 furthercomprises a throttle gas source 940 that divides into two branches 942and 944. The flow of the throttle gas within conduit branch 942 iscontrolled by controllable valve 946. Similarly, the flow of thethrottle gas within branch 944 is controlled by valve 948. Optionally,as described below, auxiliary supplies for supplying auxiliarysubstances to the juncture chamber via the gas port 932 can be provided.

The flow of throttle gas through branch 942 passes into a bubbler 950,which can be used to add a modifier liquid to the throttle gas passingthrough branch 942. Similarly, a separate liquid modifier can be addedto the throttle gas flowing through branch 944 by bubbler 952. Thethrottle gas/liquid modifier outflows from the bubblers 950 and 952 canbe controlled by outlet valves 954 and 956 respectively, after which thetwo branches 942 and 944 merge into common branch 958. The flow of thethrottle gas and modifier liquids added by bubblers 950 and 952 throughconduit 958 and eventually into juncture chamber 914 can be controlledby controllable valve 960.

The various controllable valves 946, 948, 954 and 956 enable liquidmodifiers to be added to the throttle gas by bubblers 950 and 952 in acontrolled manner to facilitate selectivity by clustering and reactingions to different degrees thereby shifting their masses observed in themass spectrometer 904. As described above, the modifiers added may alsoinclude hydrogen and deuterium exchange agents, such as deuterated wateror methanol, used, amongst other things, to count the number ofexchangeable protons on the ions prefiltered with the differentialmobility spectrometer.

In the differential mobility spectrometer/mass spectrometer systems ofFIGS. 1 to 8, the differential mobility spectrometers can be dimensionedto provide, initially, a relatively short residence time for the ionswithin the differential mobility spectrometer, and a relatively high gasflow rate of the drift gas within the differential mobilityspectrometer. This initial bias of the differential mobilityspectrometer in favor of sensitivity at the expense of selectivity canbe subsequently offset by providing a throttle gas to the juncturechambers as described above to decrease the flow rate of the drift gas.In the aspects of the embodiments illustrated in FIG. 9, the oppositeapproach is taken.

Referring to FIG. 9, there is illustrated in a schematic view adifferential mobility spectrometer/mass spectrometer system 1000 inaccordance with an aspect of ninth embodiment of the present invention.For clarity, the same reference numerals used in FIG. 1, with 800 added,are used in FIG. 9 to designate elements analogous to the elements ofFIG. 1. For brevity, the description of preceding figures, includingFIG. 1, are not repeated with respect to FIG. 9.

As shown in FIG. 9, the system 1000 is quite similar to the systems 200and 300 of FIGS. 1 and 2 respectively. However, instead of adding athrottle gas to the juncture chamber 1014, the system 1000 of FIG. 9comprises a gas outlet 1032 including a vacuum pump 1040 for drawing ableed gas out of the juncture chamber 1014. As the quantity of bleed gasdrawn out of the juncture chamber 1014 increases, the gas flow rate ofthe drift gas 1008 within the differential mobility spectrometer 1002will increase, which can diminish selectivity and resolution, while, atthe same time, increasing sensitivity. For this reason, in the system1000 of FIG. 9, the differential mobility spectrometer 1002 can bedimensioned to provide, initially, a relatively long residence time forthe ions 1022 within the differential mobility spectrometer 1002, and arelatively low gas flow rate of the drift gas 1008 within thedifferential mobility spectrometer 1002. This initial bias of thedifferential mobility spectrometer 1002 in favor of selectivity at theexpense of sensitivity can be subsequently offset by increasing a vacuumdraw provided by vacuum pump 1040 to increase the rate at which bleedgas is drawn from the juncture chamber 1014 to increase the flow rate ofthe drift gas.

The bleed gas may also be useful for DMS/MS systems where the massspectrometer inlet is sized to provide either a discontinuous gas flowinto vacuum, or a very low gas flow rate. As known in the art, a verysmall diameter orifice can provide a very low gas flow rate into thevacuum system, and an inlet diaphragm or adjustable orifice dimensionmay provide a discontinuous or variable gas flow into the massspectrometer vacuum system. Under these conditions, as described belowin more detail, the bleed gas draw can provide a continuous flow ofcarrier gas through the DMS cell regardless of the flow rate into thevacuum system of the mass spectrometer system.

For example, drawing a bleed gas from the juncture of a differentialmobility spectrometer and a mass spectrometer can be used to match thehigher flow capacity of the differential mobility spectrometer with thelower flow capacity of a low-flow, low-cost, portable mass spectrometer.Because pumping capacity can be the primary limitation in reducing thesize and weight of a mass spectrometer, this pumping capacity can besacrificed to provide a smaller mass spectrometer. To compensate forthis lower pumping capacity, a shutter can be provided at the orifice orinlet to the vacuum chamber. This shutter might have a duty cycle of,say, 1%, so that it is open for 10 milliseconds, and then closed for onesecond (1000 milliseconds), to reduce the load on the vacuum pump.

However, the flows through the differential mobility spectrometer canbe, and preferably are, continuous. Thus, to avoid turbulence or otherproblems, as shown in FIG. 9 a bleed gas can be drawn from the junctureof the differential mobility spectrometer with the mass spectrometer. Byextracting gas from this juncture region, a high fraction of thedifferential mobility spectrometer-filtered ions can enter the vacuumchamber inlet, while excess flow through the differential mobilityspectrometer can be exhausted as bleed gas. This bleed gas flow canprevent or reduce turbulence in the differential mobility spectrometerand maintain a constant differential mobility spectrometer resolution.

Referring to FIG. 10, there is illustrated in a series of graphs, theeffect of throttle gas on the resolution and peak width for a samplecontaining ephedrine and pseudoephedrine. The differential mobilityspectrometer electrode dimension was 1×10×300 mm. RF was set toapproximately 4000 V peak to peak amplitude. In each graph, CV voltageis plotted on the x axis, while original signal intensity is plotted onthe y axis normalized to the signal intensity achieved with no throttlegas provided.

As shown the compensation voltage peak width decreases (improvedselectivity) as more throttle gas is added to the juncture chamber,while sensitivity correspondingly diminishes. That is, the top trace inFIG. 10, trace 100, shows that data generated when the DMS electrode setis optimized for sensitivity, and no throttle gas is provided. In thiscase, the mobility peaks for pseudoephedrine and ephedrine are merged togive a single peak with very broad half width. As the volumetric flow ofthrottle gas increases, from the trace 102 representing a throttle gasflow rate of 0.4 L/min, to trace 104, representing a throttle gas flowrate of 0.8 L/min two distinct peaks begin to become apparent as aresult of the selectivity improvement achieved by narrowing each of themobility peaks. When the throttle gas is set to approximately 1.4 L/min,the peak centers are sufficiently resolved to achieve separation ofthese two components, although the sensitivity has decreased byapproximately a factor of 2. Further increases in the throttle gas flowprovide higher resolution, although the sensitivity loss also becomesgreater, as shown in trace 108, representing a throttle gas flow rate of1.8 L/min.

Accordingly, according to some aspects of these embodiments of thepresent invention, a throttle gas can be added to the juncture chamberuntil an acceptable compromise between sensitivity and selectivity isreached, such that sensitivity remains at a level to enable the peaks tobe discerned, while selectivity has been improved to enable the peaks tobe readily distinguished.

According to some aspects of some other embodiments of the presentinvention, in which no throttle gas is provided, but instead a bleed gasis drawn from the juncture chamber, the initial mass spectrum obtainedmay show peaks that are distinguishable, but which represent very faintsignals, given the loss of sensitivity due to the very high residencetimes within the differential mobility spectrometer. According to theseaspects of the present invention, increasing amounts of bleed gas can bedrawn from the juncture chamber to increase the gas flow rate throughthe differential mobility spectrometer, thereby reducing the residencetime of ions within the differential mobility spectrometer (theelectrode geometry having been selected to provide this long residencetime). As this occurs, the peak height will increase, representing thegreater sensitivity, but may also become broader and overlap. Byobserving this process, an operator can stop increasing the bleed gasflow rate at a point where the peaks are still readily distinguishableand sensitivity is still acceptable.

According to some aspects of various embodiments of the presentinvention, a method of operating mass spectrometer systems as definedabove is provided in which the differential mobility spectrometer ismaintained at an internal operating pressure (the curtain chamberoperating pressure), while the mass spectrometer is maintained at avacuum pressure that is substantially lower than the internal operatingpressure. The differential mobility spectrometer is also in fluidcommunication with the mass spectrometer to draw a gas flow, includingions provided to the differential mobility spectrometer, through thedifferential mobility spectrometer and into a vacuum chamber containingthe mass spectrometer. A gas flow between the differential mobilityspectrometer and the mass spectrometer can be modified to change the gasflow rate within the differential mobility spectrometer without changingthe total volumetric flow rate into the mass spectrometer. As describedabove, this gas flow rate can be modified, for example, by adding athrottle gas at a throttle gas flow rate to the gas flow between thedifferential mobility spectrometer and the mass spectrometer to decreasethe gas flow rate through the differential mobility spectrometer.Optionally, the throttle gas flow rate can be varied to vary thedecreases in the gas flow rate.

Optionally the method further comprises detecting the ions drawn intothe mass spectrometer to provide a mass spectrum. Initially, theelectrode geometry of the differential mobility spectrometer may beselected to provide good sensitivity but poor selectivity. Then, anoperator can select a selected resolution for the mass spectrum anddetermine and then adjust the gas flow rate to provide the selectedresolution. The operator can then vary the throttle gas flow rate todecrease the gas flow rate to provide the adjusted gas flow rate toprovide the selected resolution for the mass spectrum, by increasing aresidence time of the ions within the differential mobilityspectrometer. This can also have the result of decreasing sensitivitysomewhat, however.

Optionally, an outlet of the differential mobility spectrometer can beconnected to an inlet of the mass spectrometer to define an ion path oftravel for ions therebetween using a juncture chamber. In suchembodiments, the throttle gas can be directed into the juncture chamberand away from the ion path of travel to reduce disruption of the ionpath of travel by the throttle gas. Alternatively, the throttle gas cansimply be dispersed throughout the juncture chamber.

Optionally, the selected resolution for the mass spectrum and theadjusted gas flow rate for providing this selected resolution can bedetermined substantially contemporaneously. For example, these steps canbe performed substantially contemporaneously with the step of varyingthe throttle gas flow rate, whereby an operator can simply observe howthe resolution of the mass spectrum changes (along with the sensitivity)as the throttle gas flow rate is increased. Then, after an operatorreaches an acceptable resolution (while retaining acceptablesensitivity), the throttle gas flow rate can be maintained at a constantlevel, thereby determining the adjusted gas flow rate to provide theselected resolution of the mass spectrum.

According to aspects of other embodiments of the present invention,instead of supplying a throttle gas to a juncture chamber between thedifferential mobility spectrometer and the mass spectrometer, a bleedgas can be drawn from the gas flow between the differential mobilityspectrometer and the mass spectrometer at a bleed gas flow rate toincrease a gas flow rate through the differential mobility spectrometer.The bleed gas flow rate can be varied to vary the increase in the gasflow rate. That is, in embodiments in which a bleed gas is drawn fromthe gas flow between the differential mobility spectrometer and the massspectrometer, an electrode geometry of the differential mobilityspectrometer can initially be selected to provide good selectivity atthe price of poor or very poor sensitivity. Then, sensitivity can beimproved, while selectivity is diminished, by increasing the bleed gasflow rate of the bleed gas drawn from the gas flow between thedifferential mobility spectrometer and the mass spectrometer.

According to some aspects of some embodiments of the present invention,an operator can determine a selected transmission sensitivity, determinean adjusted gas flow rate to provide the selected transmissionsensitivity, and vary the bleed gas flow rate to provide the increase inthe gas flow rate to provide the adjusted gas flow rate to provide theselected transmission sensitivity. Optionally, the steps can beperformed altogether. That is, an operator can gradually increase avacuum pump speed connected to the juncture chamber to increase thebleed gas flow rate, observing at the same time from the mass spectrumhow the selected transmission sensitivity improves. Then, once anacceptable transmission sensitivity has been reached (and whileselectivity is still acceptable) the bleed gas flow rate can bemaintained to provide the adjusted gas flow rate to provide the selectedtransmission sensitivity. For example, for a given separation, anoperator may try to optimize the sensitivity by seeing how muchselectivity is required to eliminate an interference, and thenmaximizing the sensitivity while still removing the interference.

Referring to FIG. 11, there is illustrated in a schematic view, a massspectrometer system 1100 in accordance with an aspect of a tenthembodiment of the present invention. The mass spectrometer system 1100comprises a first vacuum lens element 1104 of a mass spectrometer(hereinafter generally designated mass spectrometer 1104), but does notinclude a differential mobility spectrometer. Lens element 1104 iscontained within a vacuum chamber 1127. The mass spectrometer 1104 alsocomprises mass analyzer elements 1104 a downstream from the vacuumchamber 1127. Ions can be transported through the vacuum chamber 1127and may be transported through one or more additional differentiallypumped vacuum stages prior to the mass analyzer indicated schematicallyas mass analyzer 1104 a, as described, for example, with respect to theembodiment of FIG. 1.

A heated tube 1102 can be provided upstream of vacuum chamber 1127.Similar to the plates of the differential mobility spectrometers of theembodiments described above, the heated tube 1102 can surround a driftgas 1108 that can drift from an inlet 1110 of the heated tube 1102 to anoutlet 1112 of the heated tube 1102. The outlet 1112 of the heated tube1102 can release a drift gas 1108 into a juncture chamber 1114. Thejuncture chamber 1114 defines a path of travel for ions between theheated tube 1102 and the mass spectrometer 1104. In some embodiments theoutlet of 1112 of the heated tube 1102 can be aligned with the inlet ofthe mass spectrometer 1104 to define an ion path of travel therebetween,while walls of the juncture chamber 1114 can be spaced from this path oftravel to limit interference with the ions 1122 traveling along the pathof travel.

The heated tube 1102 and juncture chamber 1114 are both contained withina curtain chamber 1118 defined by a curtain plate (boundary member) 1119and supplied with a curtain gas from a curtain gas source 1120. Thecurtain gas source 1120 can provide the curtain gas to the interior ofthe curtain chamber 1118. Ions 1122 can be provided from an ion source(not shown) and can be emitted into the curtain chamber 1118 via curtainchamber inlet 1124. The curtain gas can be supplied to the curtainchamber at a rate sufficient to provide both a curtain gas outflow outof the curtain chamber inlet, as well as a curtain gas inflow into theheated tube. The diameter of the inlet 1110 of the heated tube 1102 canbe substantially larger than a vacuum chamber inlet (or massspectrometer inlet) 1129, such that the heated tube 1102 does notrestrict gas flow. The pressure of the curtain gas within the curtainchamber 1118 can provide both a curtain gas outflow 1126 out of thecurtain gas chamber inlet 1124, as well as a curtain gas inflow 1128into the heated tube 1102, which inflow 1128 can become the drift gas1108 for carrying the ions 1122 through the heated tube 1102 and intothe juncture chamber 1114. The curtain plate 1119 may be connected to apower supply to receive an adjustable DC potential.

Similar to the embodiment of FIG. 1, the vacuum chamber 1127 can bemaintained at a much lower pressure than the curtain chamber 1118. Inaccordance with an aspect of an embodiment of the present invention, thevacuum chamber 1127 can be maintained at a pressure of 2.3 Torr viavacuum pump 1130. In an example, an internal pressure of the heated tube1102 can be maintained at a pressure of 760 Torr. As a result of thesignificant pressure difference between the curtain chamber 1118 and thevacuum chamber 1127, the drift gas 1108 can be drawn through the heatedtube 1102, the juncture chamber 1114 and vacuum chamber inlet 1129 intothe vacuum chamber 1127 and the first vacuum lens element 1104.

From the foregoing, it can be seen that the mass spectrometer system1100 of the FIG. 11 is, in some respects, quite similar to the systems200 and 300 of FIGS. 1 and 2 respectively. However, instead of adding athrottle gas to the juncture chamber 1114, the system 1100 of FIG. 11comprises a gas outlet 1132 including an additional vacuum pump 1140 fordrawing a bleed gas out of the juncture chamber 1114. The gas flow drawnfrom gas outlet 1132 by additional vacuum pump 1140 can draw a largerfraction of ions into the heated tube 1102. The increased gas flowthrough the heated tube 1102 can also lower the residence time for ionswithin the heated tube 1102, thereby lowering diffusion losses andincreasing sensitivity as mentioned above. The curtain gas flow rate canbe increased proportionately to the vacuum pump flow rate to ensure thatsufficient gas to provide an outflow from gas chamber inlet 1124.

In these respects, the system 1100 is quite similar to the system 1000of FIG. 9. However, the system 1100 differs from the system 1000 in FIG.9 in that the system 1100 does not include a differential mobilityspectrometer. Instead, the differential mobility spectrometer has simplybeen replaced with a heated tube 1102.

In accordance with an aspect of an embodiment of the invention, thesystem 1100 of FIG. 11 can also comprise a controller 1141. Controller1141 can comprise a computer processor, together with suitable userinput/output modules. In one embodiment, a user can adjust vacuum pump1140 (which can be any suitable device for drawing a gas flow) to adjusta rate at which bleed gas is drawn out of the juncture chamber 1114. Inthis embodiment, controller 1141 can monitor the rate at which vacuumpump 1140 draws bleed gas out of the juncture chamber 1114, and then cancalculate a suitable increase in curtain gas flow to be provided bycurtain gas source 1120, and can adjust a curtain gas flow meter 1121 toprovide this increase in curtain gas flow. Alternatively vacuum pump1140 can be maintained at a constant rate, and a adjustable restrictionsuch as an aperture may be located between pump 1140 and the juncturechamber. According to some embodiments, an increase in bleed gas flowrate will be matched by an equal increase in curtain gas inflow rate.According to other embodiments, recognizing that some of this increasein curtain gas inflow may increase flow 1126 out of curtain chamberinlet 1124, the curtain gas inflow may be increased by more than theincrease in the bleed gas flow rate.

According to another embodiment of the invention, vacuum pump 1140 maynot be directly controlled by an operator. Instead, an operator cancontrol vacuum pump 1140 via controller 1141, and controller 1141 couldthen determine, using for example, a computer processor, a suitablecorresponding adjustment to be made to the curtain gas flow rate.

According to some embodiments in which bleed gas is drawn from thejuncture chamber, ions may tend to follow streamlines directed out ofthe bleed gas outlet in the juncture chamber. Referring to FIG. 12,there is illustrated in a schematic diagram a portion of a massspectrometer system 1200 in accordance with an aspect of anotherembodiment of the invention. The mass spectrometer system 1200 comprisesan upstream heated tube 1202 and a juncture chamber 1214. The juncturechamber 1214 is located downstream of the heated tube 1202 to receivedrift gas entrained ions 1208 from the heated tube 1202. As illustrated,a bleed gas can be drawn through bleed gas port 1232 to increase thedrift gas flow rate of drift gas 1208 through heated tube 1202. On itsown, the gas outlet 1232 might tend to create streamlines of bleed gasthat could entrain ions and draw them out through gas port 1232. Toimpede this, a suitable electric field 1205 can be provided around thedrift gas 1208 where the drift gas 1208 enters the juncture chamber. Theelectric field can be configured to guide the entrained ions withinstreamlines drawn into a vacuum chamber (not shown) and to impede theions from being drawn by other streamlines through the bleed gas port1232. Suitable ion optical elements, known to those of skill in the art,such as, for example, a single or multiple ion lens elements with DC orRF potentials applied, can be used to provide the electric field 1205.More generally, and referring to FIG. 11, a potential difference betweenthe heated tube outlet 1112 and vacuum chamber inlet 1129 can helpdirect ions across the gap between the outlet 1112 and the massspectrometer inlet. The ions can exit the heated tube 1102, travelingon-axis with respect to the downstream inlet orifice, while the bleedgas can be drawn radially away from the inlet. In this configuration, apotential difference between the tube outlet 1112 and vacuum chamberinlet 1129 can help to keep ions moving in the axial direction with thegas flow into vacuum chamber 1127.

Experimental Results

The operation of the mass spectrometer system 1100 of FIG. 11, whichlacks a DMS, can be simulated to some extent by operating a massspectrometer system similar to the system 1100, except that this massspectrometer system comprises a DMS. This DMS can be run in transparentmode to allow all of the ions to be transmitted without discrimination,when the separation voltage is turned off, or set sufficiently low toprevent differential mobility separations, and the compensation voltageis set to 0. Additionally, in this mode of operation the DMS cansimultaneously transmit ions of both polarities and subject each toseparation based on their differential mobility constants.

According to an aspect of an embodiment of a present invention, a massspectrometer system similar to the mass spectrometer system 1000 of FIG.9 was operated in transparent mode, with separation voltage andcompensation voltage set to 0 volts. The dimensions of the tube or DMScell were 1×10×30 mm (while the cross section was rectangular for thecollection of these data, any suitable cross-section could have been beused, such as a typical circular cross section for a tube). The gas flowinto the vacuum, drawn through the tube, was 2.8 L/minute. The curtaingas inflow was set to 3.3 L/minute to provide a 0.5 L/minute outflowfrom the curtain plate. Operating this mass spectrometer system in thismanner results in the DMS cell essentially acting as a tube with twoconductive walls and two insulating walls.

Initially, the vacuum pump for drawing bleed gas from the juncturechamber was off. In this mode of operation, the DMS-MS signal providedby the mass analyzer elements downstream of the mass spectrometer wasapproximately 100000 cps (counts per second). Subsequently, after abouta minute, the vacuum pump for drawing the bleed gas out of the juncturechamber was turned on to draw an additional flow of 3.7 L/minute outfrom the juncture chamber. Adding this 3.7 L/minute bleed gas outflow,to the 2.8 L/minute gas flow through the tube resulting from thepressure differential between vacuum chamber 1127 and the internalpressure of the DMS, resulted in a total gas flow through the “tube” of6.5 L/minute. The curtain gas inflow was not increased at this point,thereby eliminating the beneficial outflow from the curtain plate.Nonetheless, the signal provided at the downstream mass analyzerelements increased to 540000 cps.

Subsequently the curtain gas inflow was re-optimized to 7.1 L/minute (totake into account the bleed gas drawn out) and to once again provide anoutflow of approximately 0.6 L/minute (7.1 L/minute inflow—6.5 L/minuteoutflow through the “tube”). As a result, the signal increased to760,000 cps. These results show significant gains when pumping at theexit of the “tube” (i.e. drawing the bleed gas out from the juncturechamber). These gains may be partially due to reduced residence time anddiffusion within the “tube” or DMS, and possibly, more significantly dueto amplifying the inlet gas flow to draw more ions into the “tube” andreduce losses at the inlet.

Similar experimental results were obtaining using this mass spectrometersystem, while varying the pump speed of the vacuum pump for drawing thebleed gas from the juncture chamber. When the vacuum pump was off, suchthat a 2.8 L/minute transport gas flow including minoxidil was drawnthrough the “tube”, the signal for a sample of minoxidil was 124,000 cpsas measured at the downstream mass analyzer element This signalintensity was improved when the bleed gas was drawn at 3.7 L/minute, toprovide a total transport gas flow through the “tube”, of 6.5 L/minute.At that transport flow rate, the signal intensity increased to 620000cps. Further improvements in the signal intensity were observed when thebleed gas flow rate was increased 4.9 L/minute to give a total transportflow rate through the “tube” of 7.7 L/minute. At that transport gas flowthrough the signal intensity increased further to 730000 cps. In all ofthese cases, the curtain gas inflow was increased directly andproportionately with the increases in bleed gas flow to provide arelatively constant curtain gas outflow out of the curtain gas chamberinlet.

While the Applicant's teachings are described in conjunction withvarious embodiments, it is not intended that the Applicant's teachingsbe limited to such embodiments.

1. A mass spectrometer system comprising: an ion conduit for receivingions from an ion source, the ion conduit having an internal operatingpressure; a boundary member defining a curtain gas chamber containingthe ion conduit; a curtain gas supply for providing a curtain gasdirected by the boundary member to an inlet of the ion conduit to dryand decluster the ions and to provide a gas flow into the ion conduit,and a curtain gas outflow out of a curtain gas chamber inlet; a massspectrometer at least partially sealed to, and in fluid communicationwith, the ion conduit for receiving the ions from the ion conduit; avacuum chamber surrounding the mass spectrometer for maintaining themass spectrometer at a vacuum pressure lower than the internal operatingpressure, such that the vacuum chamber is operable to draw the gas flowincluding the ions through the ion conduit and into the vacuum chamber;and, a gas outlet for drawing a gas outflow from the gas flow locatedbetween the ion conduit and the mass spectrometer to increase the gasflow rate through the ion conduit, the gas outlet being located betweenthe ion conduit and the mass spectrometer.
 2. The mass spectrometersystem as defined in claim 1 further comprising at least one heater forheating at least one of the curtain gas, the throttle gas, a heated zoneupstream of the inlet of the ion conduit, an inlet of the massspectrometer and the ion conduit to decluster the ions.
 3. The massspectrometer system as defined in claim 1 wherein the gas outlet isadjustable to vary the gas outflow from the gas flow and vary theincrease in the gas flow rate.
 4. The mass spectrometer system asdefined in claim 1 further comprising a juncture chamber connecting anoutlet of the ion conduit to an inlet of the mass spectrometer to definean ion path of travel therebetween, the gas outlet being located in thejuncture chamber.
 5. The mass spectrometer system as defined in claim 4wherein the outlet of the ion conduit is aligned with the inlet of themass spectrometer to transmit the ions substantially along the path oftravel to the inlet of the mass spectrometer; and, the juncture chambercomprises a side wall spaced from the path of travel.
 6. The massspectrometer system as defined in claim 1 wherein the ion conduitcomprises a differential mobility spectrometer for receiving ions fromthe ion source.
 7. The mass spectrometer system as defined in claim 1further comprising an electrical field generator for providing anelectrical field between the ion conduit and the vacuum chamber, theelectrical field generator being configured to generate an electricalfield to guide the ions into the vacuum chamber and to impede ions frombeing drawn out of the gas outlet.
 8. The mass spectrometer system asdefined in claim 1 wherein the ion conduit is a differential mobilityspectrometer.
 9. The mass spectrometer system as defined in claim 2wherein the at least one heater is operable to heat the inlet of the ionconduit to decluster the ions.
 10. The mass spectrometer system asdefined in claim 3 wherein the curtain gas supply is adjustable to varya curtain gas flow rate of the curtain gas to the inlet of the ionconduit.
 11. A mass spectrometer system as defined in claim 10, furthercomprising a system controller operable to monitor a gas outflow rate ofthe gas outflow out of the gas outlet, and to automatically adjust thecurtain gas flow rate based on the gas flow rate.
 12. A massspectrometer system as defined in claim 11 wherein the system controlleris operable to automatically increase the curtain gas flow rate when thegas outflow rate of the gas outflow out of the gas outlet increases, andis further operable to automatically decrease the curtain gas flow ratewhen the gas outflow rate of the gas outflow from the gas outletdecreases.
 13. A method of operating a mass spectrometer systemincluding an ion conduit contained in a curtain gas chamber, and a massspectrometer contained in a vacuum chamber at least partially sealed to,and in fluid communication, with, the ion conduit, the methodcomprising: a) maintaining the ion conduit at an internal operatingpressure by directing a curtain gas to an inlet of the ion conduit todry and decluster the ions and to provide a gas flow into the ionconduit; b) providing a curtain gas outflow out of a curtain gas chamberinlet of the curtain gas chamber; c) providing ions to the ion conduit;d) maintaining the mass spectrometer at a vacuum pressure lower than theinternal operating pressure to draw the gas flow including the ionsthrough the ion conduit and into the vacuum chamber; and, e) drawing ableed gas at a bleed gas flow rate from the gas flow between the ionconduit and the mass spectrometer to increase a gas flow rate throughthe ion conduit.
 14. The method as defined in claim 13 wherein e)further comprises varying the bleed gas flow rate to vary the increasein the gas flow rate.
 15. The method as defined in claim 14 furthercomprising determining a selected transmission sensitivity; determiningan adjusted gas flow rate to provide the selected transmissionsensitivity; and, varying the bleed gas flow rate to provide theincrease in the gas flow rate to provide the adjusted gas flow rate toprovide the selected transmission sensitivity.
 16. The method as definedin claim 15 wherein selecting the transmission sensitivity anddetermining the adjusted gas flow rate to provide the selectedtransmission sensitivity are substantially contemporaneous.
 17. Themethod as defined in claim 13 further comprising: providing the curtaingas at a selected volumetric flow rate to the inlet of the ion conduitto provide the gas flow through the ion conduit and into the massspectrometer, and a curtain gas outflow away from the inlet of the ionconduit and outside the ion conduit to decluster the ions; and,adjusting the selected volumetric flow rate of the curtain gas directlyand proportionately with changes in the bleed gas flow rate to maintaina substantially constant rate of the curtain gas outflow.
 18. The methodas defined in claim 13 wherein the ion conduit comprises a differentialmobility spectrometer for receiving ions from the ion source, thedifferential mobility spectrometer having electrodes and at least onevoltage source for providing DC and RF voltages to the electrodes, andthe method further comprises operating the differential mobilityspectrometer in transparent mode such that the RF voltage provided tothe electrodes is zero Volts.
 19. The method as defined in claim 18wherein the DC voltage provided to the electrodes is zero Volts.
 20. Themethod as defined in claim 13 further comprising heating the ion conduitto decluster the ions.
 21. The method as defined in claim 13 furthercomprising providing an electrical field between the ion conduit and thevacuum chamber, the electrical field being configured to guide the ionsinto the vacuum chamber and to impede ions from being drawn out of thegas flow and into the bleed gas flow.
 22. The method as defined in claim21 wherein the ion conduit is a differential mobility spectrometer, andthe method further comprises operating the differential mobilityspectrometer in transparent mode with a compensation voltage of zerovolts.
 23. The method as defined in claim 22 wherein the method furthercomprises operating the differential mobility spectrometer intransparent mode with a separation voltage of zero volts.